Rotation about anomeric bond

These results clearly indicate that barriers to all isomerisation processes are at least less than about 8kcalmol 1. In /V-benzyloxy-7V-chlorobenzamide 44 the amide isomerisation was not observable but the anomeric overlap resulted in diastereotopic benzylic hydrogens, which at coalescence afforded a barrier for rotation about the N-OBn bond of around 10.3 kcalmol-1.32 Like its /V-chloro analogue, the amide isomerisation barrier in 43 is too low to be observed by 3H NMR and even though there is definitive X-ray and theoretical evidence for anomeric effects in /V-acyloxy-/Y-alkoxyamidcs, the barrier to isomerisation about the N-OBn bond must be lower than 10.3 kcalmol-1. The n0-CN ci anomeric interaction in 44 is predicted to be stronger than the n0-CN OAc interaction in 43 on purturbation arguments.32... 

The turning of the key once the complex has formed is a separate issue. In this regard, Lemieux (47) has pointed out that rotation about the glycosidic bond must weaken the exo-anomeric effect and thereby importantly activate the anomeric carbon to nucleophilic attack. Therefore, it seems likely that the role of the key hydroxyl group of the aglycon is to accommodate the rotation prior to the attack by water to form / -D-glucopyranose, which is the first product of the reaction. 

Perhaps more disconcerting is the contention, based on the NMR studies, that sugars are not conformationally stationary in solution. Rather, there appears to be free rotation about the anomeric C-0 bond in the fructose ring of sucrose and all... 

Tvaroska, 1., Bleha, T. Collect. Czech Chem. Commun. 45, 1883 (1980) CA 94,15031a (1981) They studied the stability of the (MeO)2CH2 conformer formed by rotation about the central C-O bonds. The anomeric (gauche) effect makes the synclinal more stable than the antiperiplanar conformations. The anomeric effect disappears with increasing solvent polarity. Their results suggest that the anomeric effect still contributes to the stability of the monomer and polymer conformation in polymerization solvents such as dichloromethane... 

For some linkages, at least, it is possible to detect a substantial influence on the rotation about the glycosidic bond from the exo anomeric effect this evidence is from coupling constants (74T1933 80CJC631) and... 

Figure 1. Theoretical potential-energy curves for rotation about the anomeric bond from ah initio Hartree-Fock 431-G calculations on dimethoxymethane. is the glycosidic O-5-C-l-O-l-CH i torsion angle. is the C-5-0-5-C-1-0-1 torsion angle and is 60° for a-D-pyranosides, 180° for fl-v-pyranosides (see...

The exo-anomeric effect is illustrated in Fig. 3, which shows three staggered orientations for rotation about the glycosidic bond in both the a and p anomer of methyl D-glycopyranoside. These are referred to as -I-sc),... 

Additional evidence on the selection of conformations by the exo-ano-meric effect is derived from the solid-state structures of saccharides. It was earlier observed that the actual orientation of the anomeric alkoxyl group in pyranosides in the solid state corresponds to the (+sc, +sc) or ap, —sc) conformer, and thus proved that these conformers respectively represent the most stable axial and equatorial forms. As already noted, a particularly clear illustration of the operation of the exo-anomeric effect comes from the nonreducing disaccharide 0 ,a-trehalose, in which the most stable orientation about both exocyclic, C-0 bonds corresponds to the (+sc, +sc) conformer. Analyses of carbohydrate structures - revealed regularities in the distribution of the torsional angle O that are consistent with a restriction of rotation about the exocyclic C-O bond. The torsional angle for equatorial isomers varies from — 50° to — 110 , with a mean value of—79.4°. For the axial isomers, the range is 30-130°, with a mean value of 84.5 ° (see Ref. 29). 

In the case where the electronegative substituent at Cl is not torsionally symmetrical - as with pyranoses and pyranosides - an exactly similar effect is observed with respect to rotation about the 01—Cl bond. This is termed the exo-anomeric effect [15], and ensures that the preferred conformation of an a-glycoside is as shown the other rotamer not disfavoured by the exo-anomeric effect has R exactly under the pyranose ring, where there are severe non-bonded interactions (Fig. 4). 

There are two main manifestations of the anomeric effect concerning energy (Section IV.A) and concerning structure (Section IV.B). In this section, however, the energies of ground states are not considered further since they are an essential part of the definition of the anomeric effect. We shall deal here only with energies of transition states, in particular with transition states of chemical reactions (bond breaking) and transition states for rotation about bonds to an anomeric atom. 

The average values of J for C-1 - H-il and C-4 - H-1 and angle of rotation about the interglycosidic linkage were calculated and shown to fit the experimentally determined values. The exo-anomeric effect and intramolecular hj drogen bonding were considered unimportant. 

Lemieux, R. U., and S. Koto The Conformational Properties of Glycosidic Linkages. Tetrahedron 30, 1933 (1974) Bailey, W. F., and E. L. Eliel Conformational Analysis. XXIX. 2-Substituted and 2,2-Disubstituted 1,3-Dioxanes. The Generalized and Reverse Anomeric Effects. J. Amer. Chem. Soc. 96, 1798 (1974) Anet, F. A. L., and I. Yavari Generalized Anomeric Effect and Barrier to Internal Rotation about the Oxygen-Methylene Bond in Chloromethyl Ether. J. Amer. Chem. Soc. 99, 6752 (1977). 

The exo-anomeric effect influences the rotations aroimdthe glycosidic C-1—O bond and is therefore important in determining the relative orientations of saccharide units in carbohydrate chains. The exo-anomeric effect is a balance between electronic and steric effects. The three staggered orientations for rotation about the glycosidic bond are not equivalent the exo-anomeric effect causes preference for the +synclinal orientation of the aglycone group in the a series and -synclinal for the series (see Fig. 18 for the definition of the torsion angle domains). 

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